Finally, a tool to predict the response to chemotherapy before bladder cancer surgery

ASCO: Finally, a tool to predict the response to chemotherapy before bladder cancer surgery

Data from clinical studies conducted by the Cancer Center of the Cancer Center at the University of Colorado show that a predictive tool called COXEN may indicate which bladder cancer patients will respond to preoperative chemotherapy, allowing doctors offer such chemotherapy to patients likely to have other treatment options with patients unlikely to benefit from it. The results will be presented on Monday, June 3 at 8:00 am as an oral summary at the annual meeting of the American Society of Clinical Oncology (ASCO) of 2019 (ASCO Brief # 4506).

"The idea is that, for any individual tumor, the expression of its gene can tell us if the cancer will respond to some type of chemotherapy," said Thomas Flaig, MD, badociate dean of Clinical Research. at the University of Colorado Faculty of Medicine Research Fellow at UCHealth and National Principal Investigator of the COXEN Phase II Clinical Trial. "This is an important clinical application of a concept developed by Colorado-based researchers, which could have implications in predicting the response to chemotherapy for many types of cancer."

COXEN, which stands for Gene Analysis of Coexpression, was developed by Dan Theodorescu, former director of the UC Cancer Center, currently director of the Samuel Oschin Cancer Research Institute at Cedars-Sinai. The Thoedorescu laboratory used 60 human-derived cancer cell lines prepared by the National Cancer Institute to develop a gene expression approach to predict the sensitivity of these cells to various chemotherapies. The COXEN principle was implemented as part of the ongoing clinical trial by Dan Gustafson, PhD, a CU Cancer Center researcher and research director at Colorado State University's Flint Animal Cancer Center.

"Gustafson is very good at math and translates it into a clinical setting," says Flaig. "It was essential for this test to be operational."

The trial included 237 patients with locally advanced bladder cancer who, in accordance with standard treatment, would receive preoperative (neo-adjuvant) chemotherapy aimed at reducing cancer and eradicating any microscopic deposition outside. of the bladder to increase the patient's overall survival. . The challenge for both patients and physicians has been that there are two chemotherapy regimens approved for this indication – Gemcitabine-Cisplatin (GC) and Methotrexate-Vinblastine-Adriamycin / Doxorubicin-Cisplatin (MVAC).

"It has really been a money game between the two," Flaig said.

Then, once patients start the GC or MVAC, most but not all will respond and there is no way to predict which patients would benefit. Patients who respond to GC or MVAC have a higher risk of curative surgery; Patients who do not respond to the GC or MVAC have lost valuable time during which their cancer may actually develop before the surgery, making the success of the operation much less likely.

"If they answer, you increase your cure rate.If patients do not respond, you delay surgery.The problem is that clinicians make empirical decisions because there is no data to guide specific treatment decisions, "said Flaig. .

The current clinical trial was intended to provide this data. First, participants were randomized to receive either GC or MVAC. Then, Flaig and his colleagues collected gene expression signatures for each tumor and asked a simple question using the COXEN approach: can we predict whether the patient will respond to his chemotherapy? Specifically, physicians, including pathologist Scott Lucia, badessed whether chemotherapy resulted in a "downgrading" of the tumor at the time of surgery, and whether the surgery resulted in the removal of any detectable cancer (called "pathological T0" or complete pathological response).

While COXEN was unable to predict whether a patient was responding to the MVAC chemotherapy regimen, when the results of MVAC and GC were pooled, COXEN showed a statistically significant ability to predict which patients were responding using the GC biomarker. .

"This was not meant to be a definitive test, but rather a phase II trial that could tell us if COXEN is able to identify the responders in a prospective multicenter trial." I think the COXEN GC biomarker has very well, and we look forward to continuing our work in this area, "said Flaig.

In addition to generating COXEN signatures, tumors from the trial will be evaluated for DNA, microRNAs, SNPs, and circulating tumor cells, potentially validating new biomarkers to increase the power to predict the response to chemotherapy.

"When this trial began six or seven years ago, bladder cancer was in a different position: we had no FDA-approved drug for 30 years, and in this trial six drugs have been approved, but none of these drugs apply to neoadjuvant therapy, however, with the success of this trial and other recent trials of bladder cancer, we are increasingly optimistic about being able to design such tests for help patients with this common illness, "said Flaig.

Flaig also points out that, regardless of the outcome of the study, there is still compelling evidence to recommend cisplatin-based chemotherapy (GC or MVAC) before surgery for the treatment of bladder cancer.

"The bladder cancer research community has been mobilized to carry out this test," said Flaig. "I am honored to be part of this group that poses and answers questions of critical clinical importance to our patients."

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This story was published on: 2019-05-31. To contact the author, please use the contact information in the article.

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